The subject matter disclosed herein relates to cells grown in cell culture and distinguishing between viable and nonviable cells in cell culture in real time.
The self-replicating nature of biological systems may be harnessed to produce materials of interest by growing individual cells or organisms that produce such materials and purifying the desired products from the cell culture. For example, certain drugs or compounds may be produced by cells, either as a natural metabolic product of the cells or via engineered cells, such as cells engineered to produce recombinant proteins. These cells may be grown in large scale reactors to produce high quality biopharmaceuticals. In such reactors, the manufacturing parameters are monitored using in-line sensors and off-line (i.e., not in-line but in the laboratory, not connected to the reactors) analytical systems. Monitoring of critical manufacturing parameters may be performed upstream (before the bioreactor), in the bioreactor, and downstream (after the bioreactor). Parameters that are typically continuously monitored include parameters that influence growth conditions, such as temperature, solution conductivity, pressure, pH, glucose concentration, dissolved oxygen, and viable cell mass, and are monitored in a similar manner in both single-use and in conventional stainless steel manufacturing systems. Other parameters, such as cell viability, lactate, glutamine, osmolality, pyruvate, amino acids, product purity, and trace elements are typically not measured in-line, because of difficulties of measurements using existing sensors. Instead, these parameters are typically measured “off line” by extracting samples from the reactors and further analyzing these samples outside of the reactor using laboratory analytical instruments.